Barts Cancer Institute (BCI), supported by the Pancreatic Cancer Research Fund, are working with Spirogen and ADC Therapeutics in finding a cure for pancreatic cancer from an unlikely source – foot and mouth disease.
The virus, which wiped out more than six million sheep, cattle and pigs in the UK in 2001, harbours a protein that binds to a protein (integrin alpha-v beta-6, written avb6) that is also expressed on the majority of pancreatic cancers. The ground-breaking study uses a peptide, or protein fragment, from the virus protein that targets avb6, to deliver therapy to pancreatic cancer.
The hope is these results could lead to new therapies for a form of cancer that has the worst survival rates of all cancers; just one in twenty patients are alive five years after diagnosis.
In experiments on mice the peptide was used to ferry a highly potent drug, called tesirine, to the tumours – which were completely destroyed.
Lead author Professor John Marshall said: “Foot-and-mouth-disease virus uses avb6 as a route to infect cattle, as the virus binds to this protein on a cow’s tongue. By testing pieces of the protein in the virus that attaches to avb6, we have developed a route to deliver a drug specifically to pancreatic cancers. Our previous research had shown that 84 per cent of pancreatic cancer patients have high levels of avb6 on their cancers.”
The tests, described in the journal Theranostics, were conducted on cells grown in the laboratory and in living mice.
Genetically identical human cancer cells were used, both with and without avb6. The former were most affected when exposed to the peptide-drug conjugate. The latter needed much higher doses to be killed.
The trials in the rodents gave the most impressive results. Mice that had avb6-positive tumours only needed a tiny amount three times a week. This stopped the tumours growing.
When the dose was increased and given just twice a week, almost all these tumours disappeared completely.
Prof Marshall said: “These very exciting results, that are the result of many years of laboratory testing, offer a completely new way of treating pancreatic cancer. One advantage of targeting avb6 is that it is very specific to the cancer, because most normal human tissues have little or none of this protein. So we are hopeful that, if we can develop this into an effective treatment for pancreatic cancer, it would have limited side effects.”
Prof Marshall’s team, supported by the Pancreatic Cancer Research Fund, together with QMB tenants Spirogen and ADC Therapeutics, now want to test the treatment in more complex mice models, to see if it can stop the spread of pancreatic cancer. They then hope to move onto clinical trials.
Dr Emily Farthing, senior research information manager at Cancer Research UK, said: “Although we have made great progress in treating many types of cancer, survival remains stubbornly low for people with pancreatic cancer and there is an urgent need for more effective treatments.
“This early-stage research has developed a promising new drug that reduces the growth of pancreatic tumours in the lab. And with further research to see if it is safe and effective for patients, we hope this could one day offer new hope for people with this disease.”
Pancreatic cancer is often diagnosed late because early symptoms can be non-specific in its early stages and are often mistaken for other less lethal conditions.
Pancreatic cancer strikes 9,100 people in UK and 56,770 in the US each year. A quarter of patients with the disease die within a month of being diagnosed, and three quarters within a year.